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TWiV #79: Red hot chili viruses

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Hosts: Vincent Racaniello and Alan Dove.

On episode #79 of the podcast “This Week in Virology”, Vincent and Alan converse about making published science accessible to everyone, global eradication of poliomyelitis, and whether a plant virus can cause disease in humans.

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Is bivalent poliovirus vaccine a good idea?

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polio-immunizationA new bivalent poliovirus vaccine, consisting of infectious, attenuated type 1 and type 3 strains, has been deployed in Afghanistan. The use of this vaccine was recommended by the Advisory Committee on Poliomyelitis Eradication, the global technical advisory body of the Global Polio Eradication Initiative. Considering the polio experience in Nigeria, the elimination of type 2 poliovirus from the vaccine might have serious consequences.

There are three serotypes of poliovirus, all of which can cause poliomyelitis. Infection with one serotype of the virus does not confer protection against the other two; therefore poliovirus vaccines have always included all three serotypes (they are trivalent). The attenuated vaccine that is used in the eradication effort is an infectious vaccine. The vaccine is ingested, the viruses replicate in the intestine, and immunity develops. Viruses of all three serotypes undergo genetic changes during replication in the alimentary tract. As a consequence, the vaccine recipient excretes polioviruses that can cause paralysis. These so-called vaccine-derived polioviruses (VDPV) can cause outbreaks of poliomyelitis in non-immune people, as described in Polio among the Amish.

Poliovirus type 2 was declared eradicated from the globe by the World Health Organization in 1999. When type 2 poliovirus was eliminated, many countries began using monovalent type 1 and type 3 vaccines: one vaccine for type 1 and another for type 3. As a consequence of this immunization strategy, population immunity to type 2 poliovirus declined. Not unexpectedly, there was an outbreak of type 2 poliovirus in Nigeria in 2006. The surprise was that the outbreak was caused by a poliovirus type 2 vaccine strain.

Before 2003, the year that Nigeria began a boycott of polio immunization, the trivalent polio vaccine was used. Immunization resumed with monovalent types 1 and 3 vaccine in 2004. Therefore the source of the VDPV type 2 is most likely the trivalent vaccine used before 2003.

The press release at polioeradication.org announcing the bivalent vaccine proclaims:

Of the three wild polioviruses (known as types 1, 2 and 3), type 2 has not been seen anywhere in the world since 1999.

The statement ignores the fact that there is vaccine-derived type 2 poliovirus in the world – and it can cause polio as well as ‘wild’ poliovirus. Such strains have been isolated in Nigeria as recently as October 2009. Why isn’t the type 2 vaccine being used in Afghanistan when it is very likely that vaccine-derived type 2 poliovirus is still circulating? Just because we haven’t isolated type 2 poliovirus recently doesn’t mean that it’s gone. No type 2 poliomyelitis was detected in 1999, yet the vaccine-derived virus was silently circulating in humans.

What will be the WHO response to an outbreak of type 2 polio in Afghanistan? They will probably deploy trivalent vaccine, as was done in Nigeria in 2006. But this approach will simply lead to another cycle of eradication and emergence of type 2 polio. It’s time to begin using inactivated poliovirus vaccine, which I’ve been dreaming about for some time.

Dreaming of inactivated poliovirus vaccine

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dreamingThe World Health Organization’s global polio eradication effort uses the live, attenuated poliovirus vaccines developed by Albert Sabin. When the eradication program was announced in 1988, the goal was to eliminate global poliomyelitis, then cease immunization with poliovirus at some point in the future. In 2002 an outbreak of polio in the Dominican Republic sent a warning that this goal might not be possible. Twenty-one cases of paralytic polio were caused by a vaccine-derived poliovirus strain (VDPV). Although it had been known since the 1960s that vaccine viruses excreted by vaccinees are neurovirulent revertants, their transmission potential was unknown.

The outbreak in the Dominican Republic, and several others that were subsequently identified, made it clear that VDPV strains posed a threat to the plan to cease polio immunization. In the worst case scenario, VDPV strains would continue to circulate after vaccination had stopped, endangering the growing number of non-immune individuals. Alan Dove and I suggested, in a 1997 Science article, that it might be prudent for WHO to switch to using the inactivated poliovirus vaccine, IPV, which cannot replicate in the recipient. Once OPV usage ended, the levels of circulating VDPVs would decrease until they no longer could trigger an outbreak. Careful monitoring of VDPV in sewage would indicate when it would be safe to stop immunization with IPV.

In early 2001 I spoke at a conference on disease eradication in Washington, DC, sponsored by the Institute of Medicine. The meeting was chaired by Joshua Lederberg, and attended by the directors of polio immunization programs from many countries. I gave a presentation in which I emphasized the need to switch from OPV to IPV to avoid the problem of circulating VDPVs. This proposal received a mixed response, but I recall in particular the comments of D.A. Henderson, the architect of smallpox eradication, who said:

So, we have then say 8 years or 7 years, whatever it is to gear up to the vaccine, then another 10 years in using the inactivated vaccine. This is just totally unrealistic. We are not going to have the financial support globally for this. There is no way it is going to come about and as an end-game strategy it is dreaming to believe that this is reasonable. So, it is just not on.

I was surprised at the decisiveness of his comments, but after all, someone who has eradicated smallpox is very sure of himself.

Now WHO has now come full circle, as discussed in the Science article cited below. They agree that a transition to IPV is needed, and are looking into new ways to produce and deliver the vaccine.

And D.A. Henderson also agrees that a switch to IPV is needed. I guess I wasn’t dreaming after all.

A. W. Dove (1997). The Polio Eradication Effort: Should Vaccine Eradication Be Next? Science, 277 (5327), 779-780 DOI: 10.1126/science.277.5327.779

L. Roberts (2009). POLIO ERADICATION: Rethinking the Polio Endgame Science, 323 (5915), 705-705 DOI: 10.1126/science.323.5915.705

Eradication of Measles in South Korea

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MMWR reports on 6 April 2007 that measles has been eliminated from South Korea. The history of measles in South Korea provides a useful example of how immunization practices need to be flexible to achieve their goals.

Measles vaccine was first introduced into South Korea in 1965, and was included in the national immunization program in 1983 as part of the measles, mumps, and rubella vaccine. Two doses were given to children at 12-15 months and 4-6 years. Despite this approach, measles continued to occur, exemplified by an epidemic in 2000-2001 of 55,000 reported cases and seven deaths. Most of these infections occurred in children, indicating that vaccination was not sufficient and that circulation of measles virus continued.

In 2001, South Korea declared a goal of establishing measles by 2005, and developed key strategies, including requiring two doses of measles vaccine for school entry by 7 years of age; carrying out vaccination campaigns among children 8-16 years to cover those who were missed at an earlier age; and including laboratory confirmation of reported cases in the surveillance program.

These strategies have been very successful. Before the eradication plan, there were multiple measles epidemics in South Korea, with annual cases ranging from two to 32,647. As of November 2006, no cases of measles have occurred, and international authorities have concluded that measles has been eliminated from the country.

Measles virus still circulates in much of the world, and therfore immunization must be continued in South Korea if the disease is to be kept in check. If there is any relaxation of immunization – likely given that the infection is no longer a problem – the virus is likely to spread again.

WHO has declared that after polio is eradicated, they will turn their efforts to measles virus. While the outcome of measles immunization programs in South Korea will surely be used to promote the global effort, it will be much more difficult to eradicate the disease globally.